Lipid peroxidation products, such as 4-hydroxy-2-nonenal and malondialdehyde, have previously been shown to cause structural changes to proteins, including introduction of carbonyl groups into amino acid side chains. The level of carbonyl groups has proven to be a valuable measure of oxidative protein damage associated with aging, oxidative stress, and a number of diseases. Metal-catalyzed oxidation of glutamine synthetase and bovine serum albumin and the effect of polyunsaturated fatty acids are under investigation. For both proteins, higher levels of carbonyl derivatives are formed by ascorbate and iron when unsaturated fatty acids, such as linolenic acid, are added to the incubation mixture. Formation of carbonyl groups in bovine serum albumin in the presence of linolenic acid was simultaneous with loss of histidine and lysine residues and fragmentation. Present studies focus on the molecular mechanism of protein oxidation in the presence of lipids.